Liver cirrhosis represents the end-stage of a chronic disorder which results in severe and permanent damage of a vital organ. In recent years, liver cirrhosis was one of the leading causes of death in adults worldwide, both in males and females. The number of deaths due to cirrhosis in Europe has been estimated to be around 170,000 annually, with varying mortality rates in different European countries.
Moreover, liver cirrhosis is one of the leading diseases in disability-adjusted life years (DALYs) and has a major effect in patients’ quality of life. In addition to high mortality and impaired quality-of-life, cirrhosis is responsible for a high number of hospitalizations which are very costly and represent a high economic burden for health systems. Currently, there is no an overall therapeutic strategy based on a mechanistic approach to complications of cirrhosis. The current standard of care is clearly insufficient because mortality rate is still very high unless a liver transplant is performed.
Therefore, there is an unmet need of a therapeutic strategy that targets the main pathopysiological mechanisms of disease progression in cirrhosis that could have a significant impact on disease burden of individual patients, families, and health care systems.
Therefore, the objective of Liverhope is to evaluate a novel therapeutic strategy for patients with decompensated cirrhosis based on targeting the main pathophysiological mechanisms of disease progression in cirrhosis, namely the impairment in the gut-liver axis and the persistent hepatic and systemic inflammatory response.
This dual therapeutic approach is supported by preclinical data showing that rifaximin modulates the disturbed microbiota and decreases gut permeability and systemic endotoxin levels characteristics of cirrhosis. Moreover, simvastatin decreases systemic and hepatic inflammation, improves the altered hepatic microcirculation, decreases portal hypertension, and reduces fibrosis progression.
If successful, the therapeutic strategy proposed by LIVERHOPE, based on the combination of simvastatin and rifaximin, will have a significant impact on cirrhosis progression by:
- reducing the development of ACLF, the main causes of mortality in cirrhosis;
- reducing hospital readmissions;
- improving patients’ quality-of-life;
- reducing complications of cirrhosis;
- improving cost-effectiveness of treatment;
- increasing survival.
List of participants: